Dr. Yi Lin M.D. Ph.D. is currently a clinical hematologist at Mayo Clinic. Her long-term goal is to establish an independent academic career in translational research to identify mechanisms of tumor-mediated immune suppression, develop strategies to overcome this suppression, and test these strategies in early phase clinical trials. Her immediate goal is to generate data for a successful R01 application examining mechanisms of lymphoma-associated monocyte and tumor crosstalk that promote treatment resistance in lymphoma. Mayo Clinic has a strong cancer research program and a long track record of training successful translational and clinical researchers. Dr. Lin is supported by Mayo Clinic Cancer Center and the University of Iowa/Mayo Clinic Lymphoma SPORE to ensure adequate access to resources to complete the proposed project. Dr. Lin's K22 career development plan includes gaining competency in working with animal models and strengthening practical laboratory experience to establish an independently funded research program. In her current work, Dr. Lin has found that monocytes are commonly immune suppressive in many cancer types and contributes to aggressive disease and poor clinical outcome. Focusing on lymphoma as a tumor model, she has found that lymphoma-associated monocytes (LA-CD14) are not only immunosuppressive but also directly promote lymphoma resistance to chemotherapy. In this K22 proposal, Dr. Lin will examine mechanisms of LA-CD14 and lymphoma crosstalk that promote treatment resistance. This will be achieved through two specific aims: 1) Determine the mechanism of LA-CD14 mediated promotion of lymphoma resistance to chemotherapy. 2) Determine the mechanism of LA-CD14 mediated protection of lymphoma from anti-tumor immunity. Successful completion of this project will provide the foundational data for an R01 application to study specific strategies to re-sensitize lymphoma to chemo-immunotherapy. The NCI K22 award will provide critical support for Dr. Lin's transition from a mentored researcher to an independent investigator.